Displaying publications 21 - 40 of 98 in total

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  1. Valan A, Najid F, Chandran P, Abd Rahim AB, Chuah JA, Roslani AC
    Asian Pac J Cancer Prev, 2021 Mar 01;22(3):749-755.
    PMID: 33773538 DOI: 10.31557/APJCP.2021.22.3.749
    BACKGROUND: Malaysia is an ethnically diverse nation, comprising Malay, Chinese, Indian and indigenous groups. However, epidemiological studies on colorectal cancer have mainly focused on the three main ethnic groups. There is evidence that the clinico-pathological characteristics of some cancers may differ in indigenous populations, namely that they occur earlier and behave more aggressively. We aimed to determine if there were similar differences in colorectal cancer, focusing on the indigenous populations of Sabah.

    METHODS: Histopathological reports of all patients diagnosed with colorectal carcinoma from January 2012 to December 2016 from public hospitals in Sabah were retrieved from the central computerized database of the Pathology Department of Queen Elizabeth Hospital in Kota Kinabalu, Sabah. Supplementary data was obtained from patients' case files from each hospital. Clinico-pathological data were analysed using the IBM SPSS Statistical Software Version 23 for Windows for descriptive statistics (mean, median, ASR, AR, relative risk) and inferential statistics (Chi square test).

    RESULTS: A total of 696 patients met the inclusion criteria. The median age for colorectal cancer in Sabah was 62 years (95% CI 60.3 to 62.3), with an age specific incidence rate of 21.4 per 100 000 population. The age specific incidence rate in the indigenous populations was 26.6 per 100 000, much lower than the Chinese, at 65.0 per 100 000. The risk of colorectal cancer occurring before the age of 50 was three times higher in the indigenous population compared to the Chinese. The tumours were mainly left-sided (56.5%), adenocarcinoma in histology (98.4%) and moderately differentiated (88.7%). Approximately 79.2% of patients received curative treatment.

    CONCLUSION: Indigenous populations in Sabah develop colorectal cancer at an earlier age, and present at more advanced stages. This has implications for screening and therapeutic strategic planning. 
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    Matched MeSH terms: Colorectal Neoplasms/pathology
  2. Juhari WKW, Ahmad Amin Noordin KB, Zakaria AD, Rahman WFWA, Mokhter WMMWM, Hassan MRA, et al.
    Genes (Basel), 2021 09 20;12(9).
    PMID: 34573430 DOI: 10.3390/genes12091448
    BACKGROUND: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.

    METHOD: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.

    RESULTS: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.

    CONCLUSION: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  3. Natrah MS, Ezat S, Syed MA, Rizal AM, Saperi S
    Asian Pac J Cancer Prev, 2012;13(3):957-62.
    PMID: 22631679
    OBJECTIVE: Rapidly increasing colorectal cancer (CRC) incidence in Malaysia and the introduction of cutting edge new treatments, which prolong survival, mean that treatment outcome measures meed to be evaluated, including consideration of patient's quality of life (QoL) assessment. There are limited data on QoL in CRC patients, especially in Malaysia. Therefore, this study was performed focusing on cancer stages and age groups.

    METHODS: The cross sectional study was conducted from June to September 2011 at three public tertiary hospitals with the EORTC QLQ C-30 questionnaire in addition to face to face interview and review of medical records of 100 respondents.

    RESULTS: The mean age was 57.3 (SD 11.9) years with 56.0% are males and 44.0% females, 62% of Malay ethnicity, 30% Chinese, 7% Indian and 1% Sikh. Majority were educated up to secondary level (42%) and 90% respondents had CRC stages III and IV. Mean global health status (GHS) score was 79.1 (SD 21.4). Mean scores for functional status (physical, emotional, role, cognitive, social) rangeds between 79.5 (SD 26.6) to 92.2 (SD 13.7). Mean symptom scores (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnoea, loss of appetite) ranged between 4.00 (SD 8.58) to 20.7 (SD 30.6). Respondents role function significantly deteriorates with increasing stage of the disease (p=0.044). Females had worse symptoms of pain (p=0.022), fatigue (p=0.031) and dyspnoea (p=0.031). Mean insomnia (p=0.006) and diarrhea (p=0.024) demonstrated significant differences between age groups.

    CONCLUSION: QOL in CRC patients in this study was comparable to that in other studies done in developed countries. Pain, fatigue and dyspnoea are worse among female CRC patients. Given that functions deteriorates with advanced stage of the disease at diagnosis, a systematic screening programme to detect cases as early as possible is essential nationwide.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  4. Magaji BA, Moy FM, Roslani AC, Law CW
    Asian Pac J Cancer Prev, 2014;15(15):6059-64.
    PMID: 25124558
    BACKGROUND: Colorectal cancer is the second most frequent cancer in Malaysia. Nevertheless, there is little information on treatment and outcomes nationally. We aimed to determine the demographic, clinical and treatment characteristics of colorectal cancer patients treated at the University Malaya Medical Centre (UMMC) as part of a larger project on survival and quality of life outcomes.

    MATERIALS AND METHODS: Medical records of 1,212 patients undergoing treatment in UMMC between January 2001 and December 2010 were reviewed. A retrospective-prospective cohort study design was used. Research tools included the National Cancer Patient Registration form. Statistical analysis included means, standard deviations (SD), proportions, chi square, t-test/ ANOVA. P-value significance was set at 0.05.

    RESULTS: The male: female ratio was 1.2:1. The mean age was 62.1 (SD12.4) years. Patients were predominantly Chinese (67%), then Malays (18%), Indians (13%) and others (2%). Malays were younger than Chinese and Indians (mean age 57 versus 62 versus 62 years, p<0.001). More females (56%) had colon cancers compared to males (44%) (p=0.022). Malays (57%) had more rectal cancer compared to Chinese (45%) and Indians (49%) (p=0.004). Dukes' stage data weres available in 67%, with Dukes' C and D accounting for 64%. Stage was not affected by age, gender, ethnicity or tumor site. Treatment modalities included surgery alone (40%), surgery and chemo/radiotherapy 32%, chemo and radiotherapy (8%) and others (20%).

    CONCLUSIONS: Significant ethnic differences in age and site distribution, if verified in population-based settings, would support implementation of preventive measures targeting those with the greatest need, at the right age.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  5. Lau TP, Roslani AC, Lian LH, Chai HC, Lee PC, Hilmi I, et al.
    BMJ Open, 2014;4(8):e004930.
    PMID: 25107436 DOI: 10.1136/bmjopen-2014-004930
    To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  6. Rashid MR, Aziz AF, Ahmad S, Shah SA, Sagap I
    Asian Pac J Cancer Prev, 2009;10(6):1163-6.
    PMID: 20192604
    BACKGROUND: Colorectal cancer (CRC) is one of the major malignancies in the world. In Malaysia, CRC is fast becoming the commonest cause of cancer death. Its etiology is complex, involving both environmental and genetic factors. This study looked at the profile and outcome of five-year follow-up of patients with CRC.

    MATERIALS AND METHODS: Retrospective case review study done on CRC patients at University Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia. Patientsandapos; socio-demographic characteristics, modalities of treatment, cancer characteristics and outcome at 5-year follow up were extracted from the case records.

    RESULTS: A total of 107 case records of patients were analyzed. Peak age of CRC presentation was 40-69 years (71.1%). Male to female ratio was 1.2:1 with Chinese predominance (52.3%). Anaemia and its related symptoms including per rectal bleeding was the commonest clinical presentation. The median duration of clinical presentation was 13 weeks (IQR 21.8). More than two-thirds presented as non-emergency cases (69.2%). Most patients presented with Dukes C stage (40.2%). The overall 5-year survival rate was 40% with local recurrence rate of 19.6%. Metastasis after curative-intend treatment (surgery with adjuvant therapy) developed in 26% of patients. Lower recurrence (p = 0.016, OR = 0.205) and metastatic disease (p = 0.02, OR = 0.24) found among the Chinese patients. Almost half of the patients defaulted follow up care (43%), most often within the first year of treatment (22.4%) and the Chinese were the least likely to default (p= 0.04, OR = 0.45).

    CONCLUSION: Socio-demographic profile of CRC patients in UKMMC is comparable to Asia pacific region. Apparent delay in seeking treatment gives rise to poor overall survival and local recurrence rates.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  7. bin Sabir Husin Athar PP, bte Ahmad Norhan N, bin Saim L, bin Md Rose I, bte Ramli R
    Ann Acad Med Singap, 2008 Sep;37(9):788-3.
    PMID: 18989497
    INTRODUCTION: Metastatic adenocarcinoma from the gastrointestinal tract to the sinonasal tract is rare. The histological morphology of this lesion is indistinguishable from the colonic variant of primary sinus adenocarcinoma or intestinal-type adenocarcinoma (ITAC).

    CLINICAL PICTURE: This is a report of a case of metastatic adenocarcinoma of colorectal origin to the paranasal sinuses in a 52-year-old female who was previously treated for adenocarcinoma of the sigmoid colon. A histologic study of the surgical specimen from the sinonasal cavity demonstrated a tumour identical to the patient's prior primary tumour of the colon. The sinonasal neoplastic tissue showed marked positivity for carcinoembryonic antigen and expressed cytokeratin 20, which differentiates metastatic colonic adenocarcinoma from ITAC.

    TREATMENT/OUTCOME: The patient received palliative radiation but died 3 months after the diagnosis.

    CONCLUSION: Distinguishing metastatic adenocarcinoma from gastrointestinal tract from ITAC can be difficult. In view of the resemblance, immunohistochemical staining can help in differentiating them. It is important to recognise these as metastatic lesions as the treatment is mainly palliative.

    Matched MeSH terms: Colorectal Neoplasms/pathology*
  8. Chan SH, Ng C, Looi LM
    ANZ J Surg, 2008 Sep;78(9):775-9.
    PMID: 18844907 DOI: 10.1111/j.1445-2197.2008.04648.x
    Isosulfan blue is not available for clinical use in Malaysia. This study describes the use of methylene blue as an alternative to isosulfan blue in colorectal sentinel node mapping.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  9. Ghazali AK, Musa KI, Naing NN, Mahmood Z
    Asian J Surg, 2010 Jul;33(3):127-33.
    PMID: 21163410 DOI: 10.1016/S1015-9584(10)60022-X
    To determine the 5-year survival rate and prognostic factors for survival in patients with colorectal cancer treated at the Surgical Unit, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  10. Kok-Sin T, Mokhtar NM, Ali Hassan NZ, Sagap I, Mohamed Rose I, Harun R, et al.
    Oncol Rep, 2015 Jul;34(1):22-32.
    PMID: 25997610 DOI: 10.3892/or.2015.3993
    Apart from genetic mutations, epigenetic alteration is a common phenomenon that contributes to neoplastic transformation in colorectal cancer. Transcriptional silencing of tumor-suppressor genes without changes in the DNA sequence is explained by the existence of promoter hypermethylation. To test this hypothesis, we integrated the epigenome and transcriptome data from a similar set of colorectal tissue samples. Methylation profiling was performed using the Illumina InfiniumHumanMethylation27 BeadChip on 55 paired cancer and adjacent normal epithelial cells. Fifteen of the 55 paired tissues were used for gene expression profiling using the Affymetrix GeneChip Human Gene 1.0 ST array. Validation was carried out on 150 colorectal tissues using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) technique. PCA and supervised hierarchical clustering in the two microarray datasets showed good separation between cancer and normal samples. Significant genes from the two analyses were obtained based on a ≥2-fold change and a false discovery rate (FDR) p-value of <0.05. We identified 1,081 differentially hypermethylated CpG sites and 36 hypomethylated CpG sites. We also found 709 upregulated and 699 downregulated genes from the gene expression profiling. A comparison of the two datasets revealed 32 overlapping genes with 27 being hypermethylated with downregulated expression and 4 hypermethylated with upregulated expression. One gene was found to be hypomethylated and downregulated. The most enriched molecular pathway identified was cell adhesion molecules that involved 4 overlapped genes, JAM2, NCAM1, ITGA8 and CNTN1. In the present study, we successfully identified a group of genes that showed methylation and gene expression changes in well-defined colorectal cancer tissues with high purity. The integrated analysis gives additional insight regarding the regulation of colorectal cancer-associated genes and their underlying mechanisms that contribute to colorectal carcinogenesis.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  11. Haerian BS, Haerian MS
    Pharmacogenomics, 2015;16(4):413-25.
    PMID: 25823789 DOI: 10.2217/pgs.14.177
    There is a discrepancy between the results of 89 original studies and 15 meta-analyses investigating the association of MTHFR rs1801133 and rs1801131 polymorphisms with colorectal cancer (CRC) risk. We examined this hypothesis through meta-analyses of both loci and their diplotypes as well as evaluation of previous meta-analyses. The present meta-analysis showed that rs1801133 and rs1801131 might be CRC susceptibility variants in Americans and Australians and rs1801133 in Brazilians and Japanese. A strong linkage disequilibrium was observed between both loci and their diplotypes were associated with CRC risk. Evaluation of 15 meta-analyses showed a high discrepancy among their findings, mainly caused by population stratification of original studies and data analysis strategies in meta-analysis. Population stratification was more dominant in the studies from Australia, America and Brazil leading to false positive or negative results. In conclusion, these loci alone might modify the development of CRC in some ethnicities.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  12. Golkhalkhali B, Rajandram R, Paliany AS, Ho GF, Wan Ishak WZ, Johari CS, et al.
    Asia Pac J Clin Oncol, 2018 Jun;14(3):179-191.
    PMID: 28857425 DOI: 10.1111/ajco.12758
    AIM: Colorectal cancer patients on chemotherapy usually have elevated levels of inflammatory markers and experience numerous side effects from chemotherapy thereby leading to poor quality of life. Omega-3 fatty acid and microbial cell preparation (MCP) have been known to provide significant benefits in patients on chemotherapy. The aim of this study was to determine the effect of supplementation of omega-3 fatty acid and MCP in quality of life, chemotherapy side effects and inflammatory markers in colorectal cancer patients on chemotherapy.

    METHODS: A double-blind randomized study was carried out with 140 colorectal cancer patients on chemotherapy. Subjects were separated into two groups to receive either placebo or MCP [30 billion colony-forming unit (CFUs) per sachet] at a dose of two sachets daily for 4 weeks, and omega-3 fatty acid at a dose of 2 g daily for 8 weeks. Outcomes measured were quality of life, side effects of chemotherapy and levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein.

    RESULTS: The supplementation with MCP and omega-3 fatty acid improved the overall quality of life and alleviated certain side effects of chemotherapy. The supplementation with MCP and omega-3 fatty acid also managed to reduce the level of IL-6 (P = 0.002). There was a significant rise in the placebo group's serum TNF-α (P = 0.048) and IL-6 (P = 0.004).

    CONCLUSION: The combined supplementation with MCP and omega-3 fatty acid may improve quality of life, reduce certain inflammatory biomarkers and relieve certain side effects of chemotherapy in colorectal patients on chemotherapy.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  13. Uraoka T, Oka S, Ichihara S, Iwatate M, Tamai N, Kawamura T, et al.
    Dig Endosc, 2018 04;30 Suppl 1:36-40.
    PMID: 29658642 DOI: 10.1111/den.13060
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  14. Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  15. Gothai S, Muniandy K, Gnanaraj C, Ibrahim IAA, Shahzad N, Al-Ghamdi SS, et al.
    Biomed Pharmacother, 2018 Nov;107:1514-1522.
    PMID: 30257369 DOI: 10.1016/j.biopha.2018.08.112
    Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world according to the National Cancer Institute's latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer. Hence, in recent years, exogenous antioxidants have been immensely experimented in pre-clinical and clinical trials, considering it as a potential cure for CRC. Significantly, potential antioxidant compounds especially derivatives of medicinal plants have received great attention in the current research trend for CRC treatment. Though antioxidant compounds seem to have beneficial properties for the treatment of CRC, there are also limitations for pure compounds to be tested clinically. Therefore, this review aims to delineate the pharmacological awareness among researchers on using antioxidant compounds to treat CRC and the measures taken to prove the effectiveness of such compounds as impending drug candidates for CRC treatment in modern medication.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  16. Leong E, Ong SK, Madli F, Tan A, Lai D, Basir N, et al.
    Asian Pac J Cancer Prev, 2020 Jan 01;21(1):259-265.
    PMID: 31983194 DOI: 10.31557/APJCP.2020.21.1.259
    BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in both men and women. In most Asian countries, both the incidence and mortality rates of CRC are gradually increasing. In Brunei Darussalam, CRC ranks first and second in lifetime risk among men and women respectively. This study aims to report the overall survival rates and associated factors of CRC in Brunei Darussalam.

    METHODS: This is a retrospective study examining CRC data for the period 2007 to 2017 retrieved from a population based cancer registry in Brunei Darussalam. A total of 728 patients were included in the analysis. Kaplan Meier method was used to estimate survival rates. Univariate analysis using log-rank test was used to examine the differences in survival between groups. Multivariate analysis using Cox PH regression was used to estimate hazard of death and obtain significant predictors that influence CRC patients' survival.

    RESULTS: The median survival time for colorectal, colon and rectal cancer patients were 57.0, 85.8 and 40.0 months respectively. The overall 1-, 3- and 5- year survival rates for CRC patients were 78.0%, 57.7% and 49.6% respectively. In univariate analysis, age at diagnosis, ethnicity, cancer stage, tumour location and histology were found to have significant difference in CRC patients' survival. In the Cox PH analysis, older age (≥70 years), cancer stage, ethnicity and other histological type were determined as associated factors of CRC patients' survival.

    CONCLUSION: This study found the overall 5-year survival rate of CRC in Brunei Darussalam is similar to that in some Asian countries such as Singapore and Malaysia. However, more efforts need to be carried out in order to raise awareness of CRC and improve the survival of CRC patients.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  17. Musa M, Ouaret D, Bodmer WF
    Anticancer Res, 2020 Nov;40(11):6063-6073.
    PMID: 33109544 DOI: 10.21873/anticanres.14627
    BACKGROUND/AIM: Interactions between colorectal cancer (CRC) cells and myofibroblasts govern many processes such as cell growth, migration, invasion and differentiation, and contribute to CRC progression. Robust experimental tests are needed to investigate the nature of these interactions for future anticancer studies. The purpose of the study was to design and validate in vitro assays for studying the communication between myofibroblasts and CRC epithelial cell lines.

    MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments.

    RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion.

    CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.

    Matched MeSH terms: Colorectal Neoplasms/pathology*
  18. Rengganaten V, Huang CJ, Tsai PH, Wang ML, Yang YP, Lan YT, et al.
    Int J Mol Sci, 2020 Oct 23;21(21).
    PMID: 33114016 DOI: 10.3390/ijms21217864
    Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 and 636 circRNAs specific to the CRC parental and spheroid cells, respectively. In the CRC spheroids, algorithmic analyses unveiled a core network of mRNAs involved in modulating stemness-associated signaling pathways, driven by a circRNA-microRNA (miRNA)-mRNA axis. The two major circRNAs, hsa_circ_0066631 and hsa_circ_0082096, in this network were significantly up-regulated in expression levels in the spheroid cells. The two circRNAs were predicted to target and were experimentally shown to down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p and miR-579, confirming circRNA sponging of the targeted miRNAs. Furthermore, the affected miRNAs were demonstrated to inhibit degradation of six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 and WNT5, in the CRC spheroid cells. These mRNAs encode proteins that are reported to variously regulate the GP130/Stat, Activin/Nodal, TGF-β/SMAD or Wnt/β-catenin signaling pathways in controlling various aspects of CSC stemness. Using the CRC spheroid cell model, the novel circRNA-miRNA-mRNA axis mapped in this work forms the foundation for the elucidation of the molecular mechanisms of the complex cellular and biochemical processes that determine CSC stemness properties of cancer cells, and possibly for designing therapeutic strategies for CRC treatment by targeting CSC.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  19. Leong SW, Chia SL, Abas F, Yusoff K
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858795 DOI: 10.3390/molecules25173877
    In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure-activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  20. Hassan MR, Suan MA, Soelar SA, Mohammed NS, Ismail I, Ahmad F
    Asian Pac J Cancer Prev, 2016;17(7):3575-81.
    PMID: 27510011
    BACKGROUND: Cancer survival analysis is an essential indicator for effective early detection and improvements in cancer treatment. This study was undertaken to document colorectal cancer survival and associated prognostic factors in Malaysians.

    MATERIALS AND METHODS: All data were retrieved from the National Cancer Patient Registry Colorectal Cancer. Only cases with confirmed diagnosis through histology between the year 2008 and 2009 were included. Retrieved data include sociodemographic information, pathological features and treatment received. Survival curves were plotted using the KaplanMeier method. Univariate analysis of all variables was then made using the Logrank test. All significant factors that influenced survival of patients were further analysed in a multivariate analysis using Cox' regression.

    RESULTS: Total of 1,214 patients were included in the study. The overall 3 and 5year survival rates were 59.1% and 48.7%, respectively. Patients with localized tumours had better prognosis compared to those with advanced stage cancer. In univariate analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p=0.001) were found to be predictors of survival. None of the sociodemographic characteristics were found to exert any influence. In Cox regression analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p<0.001) were determined as independent prognostic factors of survival after adjusted for age, gender and ethnicity.

    CONCLUSIONS: The overall survival rate for colorectal cancer patients in Malaysia is similar to those in other Asian countries, with staging at diagnosis, primary tumor size, involvement of lymph node and treatment modalities having significant effects. More efforts are needed to improve national survival rates in future.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
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